Stimulation of PBMC from HIV-uninfected control donors and some HIV-infected patients with influenza A virus (Flu) results in the production of multiple anti-HIV factors that inhibit both CCR5- and CXCR4-using viral isolates prior to reverse transcription in the HIV replication cycle. These factors can be generated by CD4+ or CD8+ T cells or by monocytes. Stimulation of PBMC with allogeneic leukocytes (ALLO) also results in the production (by the same leukocyte subsets) of multiple anti-HIV factors. Efficient allo-stimulated anti-HIV factor production, but not production of the Flu-stimulated factor, is HLA associated, with the HLA-A2 allele conferring potent anti-HIV factor activity. The anti-viral activity stimulated by FLU inhibited cytomegalovirus (CMV) and HTLV-1 viral replication. The anti-viral activity stimulated by ALLO also inhibited CMV, but not HTLV-1, viral replication. The HIV-associated deficiency in IL-12 production could be circumvented in vitro by stimulating PBMC with IFN-g + CD40 ligand. Immunization of SIV-infected macaques with a poxvirus vector expressing SIV gag, pol and env genes protected against viral rebound when anti-retroviral therapy was withdrawn, and raised the possibility of this strategy for immune-based therapy. Mice transfected with the entire HIV-1 genome expressed virus in their monocytes but not in their T cells when infected with murine pathogens. The HIV-Tg mice (that have been transfected with the entire HIV-1 genome) were immunized with autologous dendritic cells (DC) that had been activated to express HIV. Both immunized wild type and HIV-Tg mice produced HIV-specific antibodies, as well as T helper and cytotoxic T lymphocyte responses, although the responses by wild type animals were stronger than those by HIV-Tg mice. This series of distinct studies raises possible avenues for immune based therapy in HIV/AIDS.